Victor Melgar's Coffee Farm

This case study focuses on a coffee farmer in Guatemala who, given current low coffee prices, is worried about his ability to maintain the family tradition of coffee production. He wonders whether the current low prices are just another of the periodic downturns in the volatile coffee market or whether the market is experiencing structural changes that will have long-term implications. In this case, the farmer is presented with three alternatives, including continuing to produce and market commodity coffee. The other alternatives involve changes in production and/or marketing practices intended to increase profit margins.Crop Production/Industries,

Changes in VO2 Kinetics After Elevated Baseline Do Not Necessarily Reflect Alterations in Muscle Force Production in Both Sexes

A link between muscle fatigue, decreased efficiency and the slow component of oxygen uptake (VO2sc) has been suggested. However, a cause-effect relationship remains to be elucidated. Although alterations in VO2 kinetics after elevated baseline work rate have previously been reported, to date no study has observed the effect on muscle force production (MFP) behavior considering physiological differences between male and female subjects. This study investigated the effect of elevated baseline work rate on the VO2 kinetics and MFP in 10 male and 10 female healthy subjects. Subjects performed 4 transitions of very-heavy (VH) intensity cycling in a randomized order after unloaded (U-VH) or moderate (M-VH) exercise. Maximal isokinetic efforts (MIE) were performed before and after each condition at two different cadences (60 or 120 rpm). Whereas baseline VO2 and time constant (τ) were significantly higher in M-VH compared to U-VH, the fundamental amplitude and the VO2 slow component (VO2sc) were significantly lower in M-VH (p < 0.05) in both sexes. Blood lactate concentration ([La]) and rate of perceived exertion (RPE) were not influenced by condition or sex (p > 0.05). The MFP post-exercise was not significantly influenced by condition in both sexes and cadences (Δtorque for males: at 60 rpm in U-VH = 13 ± 10 Nm, in M-VH = 13 ± 9 Nm; at 120 rpm in U-VH = 22 ± 14 Nm, in M-VH = 21 ± 12 Nm; for females: at 120 rpm in U-VH = 10 ± 9 Nm, in M-VH = 12 ± 8 Nm; p > 0.05), with the exception that female subjects presented smaller decreases in M-UH at 60 rpm compared to U-VH (11 ± 13 vs. 18 ± 14 Nm, respectively, p < 0.05). There was no correlation between the decrease in torque production and VO2 kinetics parameters (p > 0.05). The alterations in VO2 kinetics which have been suggested to be linked to changes in motor unit recruitment after elevated baseline work rate did not reflect alterations in MFP and fatigue in both sexes

Identification of key sequence features required for microRNA biogenesis in plants

MicroRNAs (miRNAs) are endogenous small RNAs of ∼21 nt that regulate multiple biological pathways in multicellular organisms. They derive from longer transcripts that harbor an imperfect stem-loop structure. In plants, the ribonuclease type III DICER-LIKE1 assisted by accessory proteins cleaves the precursor to release the mature miRNA. Numerous studies highlight the role of the precursor secondary structure during plant miRNA biogenesis; however, little is known about the relevance of the precursor sequence. Here, we analyzed the sequence composition of plant miRNA primary transcripts and found specifically located sequence biases. We show that changes in the identity of specific nucleotides can increase or abolish miRNA biogenesis. Most conspicuously, our analysis revealed that the identity of the nucleotides at unpaired positions of the precursor plays a crucial role during miRNA biogenesis in Arabidopsis

Full annual monitoring of Subantarctic Emiliania huxleyi populations reveals highly calcified morphotypes in high-CO2 winter conditions

Datos de investigación en: http://hdl.handle.net/10366/143074[EN]Ocean acidifcation is expected to have detrimental consequences for the most abundant calcifying phytoplankton species Emiliania huxleyi. However, this assumption is mainly based on laboratory manipulations that are unable to reproduce the complexity of natural ecosystems. Here, E. huxleyi coccolith assemblages collected over a year by an autonomous water sampler and sediment traps in the Subantarctic Zone were analysed. The combination of taxonomic and morphometric analyses together with in situ measurements of surface-water properties allowed us to monitor, with unprecedented detail, the seasonal cycle of E. huxleyi at two Subantarctic stations. E. huxleyi subantarctic assemblages were composed of a mixture of, at least, four diferent morphotypes. Heavier morphotypes exhibited their maximum relative abundances during winter, coinciding with peak annual TCO2 and nutrient concentrations, while lighter morphotypes dominated during summer, coinciding with lowest TCO2 and nutrients levels. The similar seasonality observed in both time-series suggests that it may be a circumpolar feature of the Subantarctic zone. Our results challenge the view that ocean acidifcation will necessarily lead to a replacement of heavily-calcifed coccolithophores by lightly-calcifed ones in subpolar ecosystems, and emphasize the need to consider the cumulative efect of multiple stressors on the probable succession of morphotypes.European Union's Horizon 2020, Marie Skłodowska-Curie Individual fellowshi

Full annual monitoring of Subantarctic Emiliania huxleyi populations reveals highly calcified morphotypes in high-CO2 winter conditions [Dataset]

[EN]Supplement Table S1. a. Sampling dates and morphotype relative abundance of E. huxleyi coccolith assemblages collected in the surface layer at the SOTS site. b. Sampling intervals, fluxes and morphotype relative abundance and morphometric measurements of E. huxleyi coccolith assemblages intercepted by the sediment traps at the SOTS and SAM sites. Table S2. Environmental parameters measured at the surface layer of the SOTS site from August 2011 to July 2012.European Union's Horizon 2020, Marie Skłodowska-Curie Individual fellowshipThe dataset includes Supplementary Information, Table S1. : abundance, composition and morphometric data of E. huxleyi coccolith assemblages generated during the current study Table S2: environmental data Environmental parameters measured at the surface layer of the SOTS site from August 2011 to July 2012

Characterization of Highper, an ENU-induced mouse mutant with abnormal psychostimulant and stress responses

RationaleChemical mutagenesis in the mouse is a forward genetics approach that introduces random mutations into the genome, thereby providing an opportunity to annotate gene function and characterize phenotypes that have not been previously linked to a given gene.ObjectivesWe report on the behavioral characterization of Highper, an N-ethyl-N-nitrosourea (ENU)-induced mutant mouse line.MethodsHighper and B6 control mice were assessed for locomotor activity in the open field and home cage environments. Basal and acute restraint stress-induced corticosterone levels were measured. Mice were tested for locomotor response to cocaine (5, 20, 30, and 45mg/kg), methylphenidate (30mg/kg), and ethanol (0.75, 1.25, and 1.75g/kg). The rewarding and reinforcing effects of cocaine were assessed using conditioned place preference and self-administration paradigms.ResultsHighper mice are hyperactive during behavioral tests but show normal home cage locomotor behavior. Highper mice also exhibit a twofold increase in locomotor response to cocaine, methylphenidate, and ethanol and prolonged activation of the hypothalamic–pituitary–adrenal axis in response to acute stress. Highper mice are more sensitive to the rewarding and reinforcing effects of cocaine, although place preference in Highper mice appears to be significantly influenced by the environment in which the drug is administered.ConclusionsAltogether, our findings indicate that Highper mice may provide important insights into the genetic, molecular, and biological mechanisms underlying stress and the drug reward pathway.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-012-2827-5) contains supplementary material, which is available to authorized users

Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial

Chemotherapy combined with immunotherapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for pancreatic ductal adenocarcinoma (PDAC). We conducted a randomized phase 2 trial evaluating the efficacy of nivolumab (nivo; anti-PD-1) and/or sotigalimab (sotiga; CD40 agonistic antibody) with gemcitabine/nab-paclitaxel (chemotherapy) in patients with first-line metastatic PDAC (NCT03214250). In 105 patients analyzed for efficacy, the primary endpoint of 1-year overall survival (OS) was met for nivo/chemo (57.7%, P = 0.006 compared to historical 1-year OS of 35%, n = 34) but was not met for sotiga/chemo (48.1%, P = 0.062, n = 36) or sotiga/nivo/chemo (41.3%, P = 0.223, n = 35). Secondary endpoints were progression-free survival, objective response rate, disease control rate, duration of response and safety. Treatment-related adverse event rates were similar across arms. Multi-omic circulating and tumor biomarker analyses identified distinct immune signatures associated with survival for nivo/chemo and sotiga/chemo. Survival after nivo/chemo correlated with a less suppressive tumor microenvironment and higher numbers of activated, antigen-experienced circulating T cells at baseline. Survival after sotiga/chemo correlated with greater intratumoral CD4 T cell infiltration and circulating differentiated CD4 T cells and antigen-presenting cells. A patient subset benefitting from sotiga/nivo/chemo was not identified. Collectively, these analyses suggest potential treatment-specific correlates of efficacy and may enable biomarker-selected patient populations in subsequent PDAC chemoimmunotherapy trials

Prevalence of DDC genotypes in patients with aromatic L-amino acid decarboxylase (AADC) deficiency and in silico prediction of structural protein changes

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive genetic disorder affecting the biosynthesis of dopamine, a precursor of both norepinephrine and epinephrine, and serotonin. Diagnosis is based on the analysis of CSF or plasma metabolites, AADC activity in plasma and genetic testing for variants in the DDC gene. The exact prevalence of AADC deficiency, the number of patients, and the variant and genotype prevalence are not known. Here, we present the DDC variant (n = 143) and genotype (n = 151) prevalence of 348 patients with AADC deficiency, 121 of whom were previously not reported. In addition, we report 26 new DDC variants, classify them according to the ACMG/AMP/ACGS recommendations for pathogenicity and score them based on the predicted structural effect. The splice variant c.714+4A>T, with a founder effect in Taiwan and China, was the most common variant (allele frequency = 32.4%), and c.[714+4A>T];[714+4A>T] was the most common genotype (genotype frequency = 21.3%). Approximately 90% of genotypes had variants classified as pathogenic or likely pathogenic, while 7% had one VUS allele and 3% had two VUS alleles. Only one benign variant was reported. Homozygous and compound heterozygous genotypes were interpreted in terms of AADC protein and categorized as: i) devoid of full-length AADC, ii) bearing one type of AADC homodimeric variant or iii) producing an AADC protein population composed of two homodimeric and one heterodimeric variant. Based on structural features, a score was attributed for all homodimers, and a tentative prediction was advanced for the heterodimer. Almost all AADC protein variants were pathogenic or likely pathogenic

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11